Fructose-induced prediabetes causes persistent DNA methylation changes in white adipose tissue despite metabolic...

Area of Science:

• Metabolomics and Epigenetics
• Endocrinology and Metabolic Health

Background:

• White adipose tissue (WAT) is a crucial endocrine organ for metabolic regulation.
• Epigenetic mechanisms, particularly DNA methylation, are implicated in early metabolic dysfunction.
• The role of DNA methylation in prediabetes and its reversibility is not well understood.

Purpose of the Study:

• To investigate genome-wide DNA methylation patterns in visceral WAT of prediabetic rats.
• To assess the impact of dietary normalization on these methylation changes.
• To identify specific genes and pathways affected by DNA methylation alterations.

Main Methods:

• Induction of a prediabetic state in rats using a fructose-rich diet.
• Whole Genome Bisulfite Sequencing (WGBS) to identify differentially methylated CpG sites in visceral WAT.
• Analysis of gene expression using RT-qPCR and pathway enrichment analysis.

Main Results:

• Fructose consumption led to a prediabetic phenotype and significant DNA methylation changes in visceral WAT.
• 1,151 differentially methylated CpG sites were identified, with 330 genes enriched in oxidative phosphorylation and thermogenesis pathways.
• Despite successful metabolic normalization, a subset of methylation alterations persisted, affecting genes like Kdm4c, Ces1f, and Uxs1.

Conclusions:

• Fructose-induced prediabetes causes persistent DNA methylation changes in visceral WAT.
• These persistent epigenetic alterations may contribute to the early stages of metabolic disturbances leading to type 2 diabetes.
• Dietary interventions may not fully reverse all epigenetic changes associated with metabolic dysfunction.